tbuckley/cabot-search huggingface dataset:
Dietary Protein Sources, Mediating Biomarkers, and Incidence of Type 2 Diabetes: Findings From the Women’s Health Initiative and the UK Biobank
Authors: Jie Li, Andrea J. Glenn, Qingling Yang, Ding Ding, Lingling Zheng, Wei Bao, Jeannette Beasley, Erin LeBlanc, Kenneth Lo, JoAnn E. Manson, Lawrence Philips, Lesley Tinker, Simin Liu
Journal: Diabetes Care (2022)

OBJECTIVE Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS We included 108,681 postmenopausal women without T2D at baseline from the Women’s Health Initiative (WHI) (primary cohort) and 34,616 adults without T2D from the U.K. Biobank (UKB) (replication cohort). Cox proportional hazard models were used for estimation of protein-T2D associations. Mediation analysis was performed to assess the mediating roles of biomarkers in case-control studies nested in the WHI. RESULTS In the WHI, 15,842 incident T2D cases were identified during a median follow-up of 15.8 years. Intake of animal protein was associated with increased T2D risk (hazard ratio in comparing the highest to the lowest quintile = 1.31 [95% CI 1.24–1.37]) and plant protein with decreased risk (0.82 [0.78–0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk and whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for BMI. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (0.79 [0.74–0.84]), which was mediated by levels of hs-CRP, interleukin-6, leptin, and SHBG. CONCLUSIONS Findings from these two large prospective cohorts support the notion that substituting plant protein for animal protein may decrease T2D risk mainly by reducing obesity-related inflammation.
Rise of the Clones: Myelodysplastic Syndrome to Secondary Acute Myeloid Leukemia
Authors: Kyle A. Romine, Peter van Galen
Journal: Blood Cancer Discovery (2022)

Myelodysplastic syndrome (MDS) describes a family of blood disorders driven by the clonal expansion of mutated blood cells that can evolve into secondary acute myeloid leukemia (sAML). Two new studies use single-cell and deep sequencing to elucidate the progression of MDS to AML, revealing discrete clonal architectures and the driving role of signaling mutations.
SDHA/B reduction promotes hepatocellular carcinoma by facilitating the deNEDDylation of cullin1 and stabilizing YAP/TAZ
Authors: Tao Yuan, Tianyi Zhou, Meijia Qian, Jiamin Du, Yue Liu, Jia'er Wang, Yonghao Li, Guanghan Fan, Fangjie Yan, Xiaoyang Dai, Xiawei Li, Yulian Wu, Xin Dong, Qiaojun He, Hong Zhu, Bo Yang
Journal: Hepatology (2022)

Background and Aims: Succinate dehydrogenase enzyme (SDH) is frequently diminished in samples from patients with hepatocellular carcinoma (HCC), and SDH reduction is associated with elevated succinate level and poor prognosis in patients with HCC. However, the underlying mechanisms of how impaired SDH activity promotes HCC remain unclear. Approach and Results: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury–induced murine HCC models and patient samples. Subsequent RNA sequencing, hematoxylin and eosin staining, and immunohistochemistry analyses of HCC samples revealed that Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. YAP/TAZ stability was greatly enhanced in SDHA/B‐depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation, which facilitated the deNEDDylation of cullin1 and therefore disrupted the E3 ubiquitin ligase SCF β‐TrCP complex, consequently leading to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. Conclusions: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus binding SDH‐deficient HCC cells to YAP/TAZ pathway and rendering these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in patients with HCC displaying reduced SDHA/B or elevated succinate levels.
Computational Methods for Single-Cell DNA Methylome Analysis
Authors: Waleed Iqbal, Wanding Zhou
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Dissecting intercellular epigenetic differences is key to understanding tissue heterogeneity. Recent advances in single-cell DNA methylome profiling have presented opportunities to resolve this heterogeneity at the maximum resolution. While these advances enable us to explore frontiers of chromatin biology and better understand cell lineage relationships, they pose new challenges in data processing and interpretation. This review surveys the current state of computational tools developed for single-cell DNA methylome data analysis. We discuss critical components of single-cell DNA methylome data analysis, including data preprocessing, quality control, imputation, dimensionality reduction, cell clustering, supervised cell annotation, cell lineage reconstruction, gene activity scoring, and integration with transcriptome data. We also highlight unique aspects of single-cell DNA methylome data analysis and discuss how techniques common to other single-cell omics data analyses can be adapted to analyze DNA methylomes. Finally, we discuss existing challenges and opportunities for future development.
Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks
Authors: Xu-Sheng Zhang, Jason J. Ong, Louis Macgregor, Tatiana G. Vilaplana, Simone T. Heathcock, Miranda Mindlin, Peter Weatherburn, Ford Hickson, Michael Edelstein, Sema Mandal, Peter Vickerman
Journal: The Lancet Regional Health - Europe (2022)

Despite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks.A HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated.R0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination.Although highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks.NIHR.
Comparison of Preoperative Imaging Modalities for the Assessment of Malignant Potential of Pancreatic Cystic Lesions
Authors: Sang-Woo Lee, Sung Ryul Shim, Shin Young Jeong, Seong-Jang Kim
Journal: Clinical Nuclear Medicine (2022)

The aims of this study are to compare the performance of various preoperative imaging modalities for assessing the malignant potential of pancreatic cystic lesions (PCLs) through a network meta-analysis (NMA) and to clarify the role of 18 F-FDG PET in the management of patients with PCL.PubMed, EMBASE, and Cochrane Library were searched for the studies evaluating the performance of preoperative imaging modalities for identifying malignant PCLs. The NMA was performed for 4 representative categories of various imaging modalities in terms of diagnostic performance for differentiating malignant from benign PCL and intraductal papillary mucinous neoplasms only as a subgroup analysis. To calculate the probability of each imaging modality being the most effective diagnostic method, the surface under the cumulative ranking curve values were obtained.A total of 1018 patients from 17 direct comparison studies using 2 or more preoperative imaging modalities were included for differentiating malignant from benign PCL. The positive predictive value (PPV) and accuracy of 18 F-FDG PET were significantly higher than that of CT (PPV: odds ratio [OR], 2.66; 95% credible interval [CrI], 1.21-6.17; accuracy: OR, 2.63; 95% CrI, 1.41-5.38) or MRI (PPV: OR, 2.50; 95% CrI, 1.09-6.26; accuracy: OR, 2.50; 95% CrI, 1.28-5.47) in all PCLs, as well as in the subgroup analysis for intraductal papillary mucinous neoplasm only. 18 F-FDG PET showed the highest surface under the cumulative ranking curve values in all diagnostic performance areas of sensitivity, specificity, PPV, negative predictive value, and accuracy, followed by MRI or CT.The results from this NMA suggest that 18 F-FDG PET is the best preoperative imaging modality for differentiating malignant from benign PCLs and that it can be used for the preoperative evaluation of PCLs.
Beta-adrenergic drugs and risk of Parkinson’s disease: A systematic review and meta-analysis
Authors: Ambrish Singh, Salman Hussain, Sreelatha Akkala, Jitka Klugarová, Andrea Pokorná, Miloslav Klugar, E. Haydn Walters, Ingrid Hopper, Julie A. Campbell, Bruce Taylor, Benny Antony
Journal: Ageing Research Reviews (2022)
Nanomedicines and cell-based therapies for embryonal tumors of the nervous system
Authors: Souhaila H. El Moukhtari, Elisa Garbayo, Ana Fernández-Teijeiro, Carlos Rodríguez-Nogales, Patrick Couvreur, María J. Blanco-Prieto
Journal: Journal of Controlled Release (2022)

Embryonal tumors of the nervous system are neoplasms predominantly affecting the pediatric population. Among the most common and aggressive ones are neuroblastoma (NB) and medulloblastoma (MB). NB is a sympathetic nervous system tumor, which is the most frequent extracranial solid pediatric cancer, usually detected in children under two. MB originates in the cerebellum and is one of the most lethal brain tumors in early childhood. Their tumorigenesis presents some similarities and both tumors often have treatment resistances and poor prognosis. High-risk (HR) patients require high dose chemotherapy cocktails associated with acute and long-term toxicities. Nanomedicine and cell therapy arise as potential solutions to improve the prognosis and quality of life of children suffering from these tumors. Indeed, nanomedicines have been demonstrated to efficiently reduce drug toxicity and improve drug efficacy. Moreover, these systems have been extensively studied in cancer research over the last few decades and an increasing number of anticancer nanocarriers for adult cancer treatment has reached the clinic. Among cell-based strategies, the clinically most advanced approach is chimeric-antigen receptor (CAR) T therapy for both pathologies, which is currently under investigation in phase I/II clinical trials. However, pediatric drug research is especially hampered due not only to ethical issues but also to the lack of efficient pre-clinical models and the inadequate design of clinical trials. This review provides an update on progress in the treatment of the main embryonal tumors of the nervous system using nanotechnology and cell-based therapies and discusses key issues behind the gap between preclinical studies and clinical trials in this specific area. Some directions to improve their translation into clinical practice and foster their development are also provided.
Food to Overcome Outcomes Disparities: A Randomized Controlled Trial of Food Insecurity Interventions to Improve Cancer Outcomes
Authors: Francesca Gany, Irina Melnic, Minlun Wu, Yuelin Li, Jackie Finik, Julia Ramirez, Victoria Blinder, Margaret Kemeny, Elizabeth Guevara, Caroline Hwang, Jennifer Leng
Journal: Journal of Clinical Oncology (2022)

Food insecurity is prevalent among low-income immigrant and minority patients with cancer. To our knowledge, this randomized controlled trial is the first to prospectively examine the impact on cancer outcomes of food insecurity interventions, with the goal of informing evidence-based interventions to address food insecurity in patients with cancer.A three-arm randomized controlled trial was conducted among food-insecure (18-item US Department of Agriculture Household Food Security Survey Module score ≥ 3) patients with cancer (N = 117) at four New York City safety net cancer clinics. Arms included a hospital cancer clinic-based food pantry (arm 1), food voucher plus pantry (arm 2), and home grocery delivery plus pantry (arm 3). Treatment completion (primary outcome) and full appointment attendance were assessed at 6 months. Food security status, depression symptoms (Patient Health Questionnaire-9), and quality-of-life scores (Functional Assessment of Cancer Therapy-General) were assessed at baseline and at 6 months.Voucher plus pantry had the highest treatment completion rate (94.6%), followed by grocery delivery plus pantry (82.5%) and pantry (77.5%; P = .046). Food security scores improved significantly in all arms, and Patient Health Questionnaire-9 and Functional Assessment of Cancer Therapy-General scores improved significantly in the pantry and delivery plus pantry arms.Our findings in this preliminary study suggest that voucher plus pantry was the most effective intervention at improving treatment completion, and it met our a priori criterion for a promising intervention (≥ 90%). All interventions demonstrated the potential to improve food security among medically underserved, food-insecure patients with cancer at risk of impaired nutrition status, reduced quality of life, and poorer survival. All patients with cancer should be screened for food insecurity, with evidence-based food insecurity interventions made available.
Immune Cell Signatures to Stratify Patients With Systemic Autoimmune Diseases: A Step Toward Individualized Medicine?
Authors: Takahisa Gono, Divi Cornec
Journal: Arthritis & Rheumatology (2022)

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NCCN News
Journal: Journal of the National Comprehensive Cancer Network (2022)

Guidance for COVID-19 Vaccination From NCCN Recommends Fifth mRNA Shot (Second Booster Dose) for Immunocompromised People On April 27th, 2022, NCCN released the latest recommendations from the NCCN Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis.The frequently updated guidance, along with other important information on COVID-19 and cancer, is available for free at NCCN.org/covid-19."This guidance is intended to let cancer care providers know not only what they can do, but also what they should do, according to experts across the United States," said Brahm Segal, MD, Roswell Park Comprehensive Cancer Center, Co-Leader of the NCCN Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis.The NCCN Advisory Committee is comprised of leading multidisciplinary physicians from across NCCN Member Institutions, with particular expertise in infectious diseases, vaccine development and delivery, cancer management, and medical ethics.The group first published guidance on vaccinating people with cancer against COVID-19 in January 2021 and has published numerous updates since then.The recommendations reflect the policies that have already been put in place in many of the country's top academic cancer centers.
Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by Neisseria meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province, Italy, December 2019 to January 2020
Authors: Cecilia Fazio, Laura Daprai, Arianna Neri, Marcello Tirani, Paola Vacca, Milena Arghittu, Luigina Ambrosio, Danilo Cereda, Maria Gramegna, Annapina Palmieri, Anna Carannante, Maria Rosa Bertoli, Lucia Crottogini, Giorgio Gennati, Eugenia Quinz, Livia Trezzi, Andrea Ciammaruconi, Silvia Fillo, Antonella Fortunato, Giovanni Rezza, Florigio Lista, Paola Stefanelli
Journal: Eurosurveillance (2022)

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain.
Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia
Authors: Ming Yu, Helen R. Moinova, Amber Willbanks, Victoria K. Cannon, Ting Wang, Kelly Carter, Andrew Kaz, Deepti Reddi, John Inadomi, Georg Luebeck, Prasad G. Iyer, Marcia I. Canto, Jean S. Wang, Nicholas J. Shaheen, Prashanti N. Thota, Joseph E. Willis, Thomas LaFramboise, Amitabh Chak, Sanford D. Markowitz, William M. Grady
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE). Experimental Design: DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing. Ultrasensitive methylation-specific droplet digital PCR and next-generation sequencing (NGS)-based bisulfite-sequencing assays were developed to detect the methylation level of candidate CpGs in independent esophageal biopsy and endoscopic brushing samples. Results: Five candidate methylation markers were significantly hypermethylated in HGD/EAC samples compared with SQ or NDBE (P &amp;lt; 0.01) in both esophageal biopsy and endoscopic brushing samples. In an independent set of brushing samples used to construct biomarker panels, a four-marker panel (model 1) demonstrated sensitivity of 85.0% and 90.8% for HGD and EACs respectively, with 84.2% and 97.9% specificity for NDBE and SQ respectively. In a validation set of brushing samples, the panel achieved sensitivity of 80% and 82.5% for HGD and EAC respectively, at specificity of 67.6% and 96.3% for NDBE and SQ samples. Conclusions: A novel DNA methylation marker panel differentiates HGD/EAC from SQ/NDBE. DNA-methylation–based molecular assays hold promise for the detection of HGD/EAC using esophageal brushing samples.
Opioid versus opioid-free analgesia after surgical discharge: a systematic review and meta-analysis of randomised trials
Authors: Julio F Fiore, Charbel El-Kefraoui, Marc-Aurele Chay, Philip Nguyen-Powanda, Uyen Do, Ghadeer Olleik, Fateme Rajabiyazdi, Araz Kouyoumdjian, Alexa Derksen, Tara Landry, Alexandre Amar-Zifkin, Amy Bergeron, Agnihotram V Ramanakumar, Marc Martel, Lawrence Lee, Gabriele Baldini, Liane S Feldman
Journal: The Lancet (2022)
European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases
Authors: Daniël A. Korevaar, Sara Colella, Markus Fally, Juliette Camuset, Thomas V. Colby, Lars Hagmeyer, Juergen Hetzel, Fabien Maldonado, Antonio Morais, Claudia Ravaglia, René Spijker, Sara Tomassetti, Lauren K. Troy, Johny A. Verschakelen, Athol U. Wells, Thomy Tonia, Jouke T. Annema, Venerino Poletti
Journal: European Respiratory Journal (2022)

Background In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. Methods The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. Results In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. Conclusions TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly “very low”.
Tumor-microenvironment triggered signal-to-noise boosting nanoprobes for NIR-IIb fluorescence imaging guided tumor surgery and NIR-II photothermal therapy
Authors: Peiyuan Wang, Jiaqi Li, Min Wei, Ruiqin Yang, Kangliang Lou, Yongying Dang, Wen Sun, Fangqin Xue, Xiaolong Liu
Journal: Biomaterials (2022)